- Email: [email protected]
241. Influence of Prenatal Maternal Depression on Amygdala-Prefrontal Circuits in Infant
Biological Psychiatry
Thursday Abstracts
Background: Most resting-state functional connectivity (rs-FC) studies in PTSD have not examined the hippocampus as their primary seed region, while also referring to it as a singular structure, whereas research has clearly shown a dissociation between posterior and anterior hippocampal connectivity. PTSD research has also overlooked age-related differences in anterior and posterior hippocampus connectivity. Here we examined whether PTSD patients and trauma-exposed healthy controls (TEHCs) exhibit differential rs-FC of anterior and posterior hippocampus with key brain regions implicated in PTSD. We also explored the association between age and rs-FC in PTSD. Methods: Rs-FC analysis was performed using two seed regions of interest (ROIs; anterior and posterior hippocampus) and five target ROIs (amygdala, insula, medial prefrontal cortex, posterior cingulate cortex (PCC) and precuneus) among 48 PTSD patients and 34 matched controls. Results: A group-by-hippocampus interaction was found for the precuneus (p,0.025) and PCC (p50.05) pathways. Post-hoc analyses revealed a pathologic loss of anterior to posterior connectivity differentiation between the hippocampus and the precuneus and the PCC in PTSD compared to controls (p,0.001 and p50.016, respectively). The PTSD group also demonstrated a lower negative connectivity of the posterior hippocampusprecuneus pathway compared with the TEHC group (p50.0076). Among PTSD patients, increased age had the effect of normalizing posterior hippocampus-precuneus and -PCC connectivity (r520.34, p50.018; r520.303, p50.036, respectively), whereas no such effect was noted for the control group. Conclusions: PTSD is characterized by an aberrant differentiation of anterior and posterior hippocampus connectivity with the precuneus and PCC, a pattern that appears to diminish with increasing age. Supported By: R01MH072833 Keywords: Hippocampus, PTSD - Posttraumatic Stress Disorder, Resting state functional connectivity, Age
241. Influence of Prenatal Maternal Depression on Amygdala-Prefrontal Circuits in Infant Jiook Cha1, Jonathan Posner1, Amy Roy2, Brad Peterson3, Hanna Gustafsson1, Elizabeth Raffanello1, Jay Gingrich1, and Catherine Monk1 1 3
Columbia University Medical Center, 2Fordham University, USC
Background: Prenatal exposure to maternal depression is common and puts offspring at risk for developing a range of neuropsychiatric disorders. Despite its prevalence and adverse associations, neurobiological processes by which prenatal maternal depression (PMD) confers risk remain unclear. Methods: We assessed maternal mood and fetal behavior between 34 and 37 gestational weeks. After birth, we collected resting-state (sleep) functional magnetic resonance imaging (fMRI) and diffusion MRI in 64 infants (mean age55.861.7 weeks) with (n520) and without (n544) in utero exposure to PMD. We investigated functional and structural connectivity within amygdala–prefrontal circuits.
Results: We found atypical amygdala–prefrontal connectivity in PMD-exposed infants. Resting fMRI indicated increased an inverse correlation between the amygdala and the dorsal prefrontal cortex (PFC), bilaterally. A sophisticated timeseries analysis using dynamic causal modeling showed, in PMDexposed infants, a stronger excitatory influence from the amygdala to the PFC, and a weaker excitatory influence from the PFC to the amygdala, compared with controls. Diffusion tractography indicated a decreased connection strength between the right amygdala and the right ventral PFC. Last, path analyses supported a mechanistic account relating prenatal maternal depression to a third-trimester fetal behavior: PMD affects amygdala–PFC connectivity, which in turn, correlates with an increase in fetal heart rate reactivity to in utero perturbation. Conclusions: This study suggests that the maturation and coordination of central and peripheral physiology are affected by prenatal exposure to maternal depression. It also supports the notion that PMD-associated variations in the development of amygdala–PFC circuits are relevant for future neurobehavioral maturation. Supported By: NIMH grant P05-MH090966 Keywords: Maternal Depression, neonatal, Amygdala, PFC, heart rate reactivity
242. Superficial White Matter Integrity in Autism Spectrum Disorders Marc-Antoine d'Albis1, Pamela Guevara2, Miguel Guevara2, Jean-François Mangin3, Cyril Poupon3, Duclap Delphine3, Laidi Charles4, Jennifer Boigontier5, Marion LEBOYER6, and Josselin Houenou7 APHP-France, 2Universidad de Conception, Chile, 3Neurospin, CEA, France, 4Inserm U955 eq15, Fondation FondaMental, GHU Mondor, Neurospin, CEA, France, 5Inserm U955 eq15, Fondation FondaMental, GHU Mondor, Neurospin, CEA,France, 6Inserm U955 eq15, Fondation FondaMental, GHU Mondor, France, 7Inserm U955 eq15, Fondation FondaMental, GHU Mondor, Neurospin, CEAFrance 1
Background: Autism spectrum disorders (ASD) are characterized by an atypical brain growth and abnormalities in the anatomical and functional connectivity. These abnormalities have been identified in the long-distance tracts (antero-posterior fasciculi, corpus callosum). Very few studies have explored shortdistance tracts (cortico-cortical U-shaped fibers), despite their importance in the local connectivity (between adjacent cortical gyri) and in the cognitive functions. Our work aims to study shortdistance anatomical connectivity in ASD subjects compared to controls. Methods: We included thirty ASD subjects and forty male controls without mental retardation. The subjects benefited from a 3T MRI (Neurospin), with anatomical and diffusion weighted sequences. We performed a whole brain tractography (Connectomist 2.0) and automatically segmented 63 short tracts. For each fasciculus, we extracted mean gFA (generalized Fractional Anisotropy), MD (Mean Diffusivity), AD (Axial Diffusivity) and RD (Radial Diffusivity). An ANCOVA was performed with gFA
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal
S99
Thursday Abstracts
Background: Most resting-state functional connectivity (rs-FC) studies in PTSD have not examined the hippocampus as their primary seed region, while also referring to it as a singular structure, whereas research has clearly shown a dissociation between posterior and anterior hippocampal connectivity. PTSD research has also overlooked age-related differences in anterior and posterior hippocampus connectivity. Here we examined whether PTSD patients and trauma-exposed healthy controls (TEHCs) exhibit differential rs-FC of anterior and posterior hippocampus with key brain regions implicated in PTSD. We also explored the association between age and rs-FC in PTSD. Methods: Rs-FC analysis was performed using two seed regions of interest (ROIs; anterior and posterior hippocampus) and five target ROIs (amygdala, insula, medial prefrontal cortex, posterior cingulate cortex (PCC) and precuneus) among 48 PTSD patients and 34 matched controls. Results: A group-by-hippocampus interaction was found for the precuneus (p,0.025) and PCC (p50.05) pathways. Post-hoc analyses revealed a pathologic loss of anterior to posterior connectivity differentiation between the hippocampus and the precuneus and the PCC in PTSD compared to controls (p,0.001 and p50.016, respectively). The PTSD group also demonstrated a lower negative connectivity of the posterior hippocampusprecuneus pathway compared with the TEHC group (p50.0076). Among PTSD patients, increased age had the effect of normalizing posterior hippocampus-precuneus and -PCC connectivity (r520.34, p50.018; r520.303, p50.036, respectively), whereas no such effect was noted for the control group. Conclusions: PTSD is characterized by an aberrant differentiation of anterior and posterior hippocampus connectivity with the precuneus and PCC, a pattern that appears to diminish with increasing age. Supported By: R01MH072833 Keywords: Hippocampus, PTSD - Posttraumatic Stress Disorder, Resting state functional connectivity, Age
241. Influence of Prenatal Maternal Depression on Amygdala-Prefrontal Circuits in Infant Jiook Cha1, Jonathan Posner1, Amy Roy2, Brad Peterson3, Hanna Gustafsson1, Elizabeth Raffanello1, Jay Gingrich1, and Catherine Monk1 1 3
Columbia University Medical Center, 2Fordham University, USC
Background: Prenatal exposure to maternal depression is common and puts offspring at risk for developing a range of neuropsychiatric disorders. Despite its prevalence and adverse associations, neurobiological processes by which prenatal maternal depression (PMD) confers risk remain unclear. Methods: We assessed maternal mood and fetal behavior between 34 and 37 gestational weeks. After birth, we collected resting-state (sleep) functional magnetic resonance imaging (fMRI) and diffusion MRI in 64 infants (mean age55.861.7 weeks) with (n520) and without (n544) in utero exposure to PMD. We investigated functional and structural connectivity within amygdala–prefrontal circuits.
Results: We found atypical amygdala–prefrontal connectivity in PMD-exposed infants. Resting fMRI indicated increased an inverse correlation between the amygdala and the dorsal prefrontal cortex (PFC), bilaterally. A sophisticated timeseries analysis using dynamic causal modeling showed, in PMDexposed infants, a stronger excitatory influence from the amygdala to the PFC, and a weaker excitatory influence from the PFC to the amygdala, compared with controls. Diffusion tractography indicated a decreased connection strength between the right amygdala and the right ventral PFC. Last, path analyses supported a mechanistic account relating prenatal maternal depression to a third-trimester fetal behavior: PMD affects amygdala–PFC connectivity, which in turn, correlates with an increase in fetal heart rate reactivity to in utero perturbation. Conclusions: This study suggests that the maturation and coordination of central and peripheral physiology are affected by prenatal exposure to maternal depression. It also supports the notion that PMD-associated variations in the development of amygdala–PFC circuits are relevant for future neurobehavioral maturation. Supported By: NIMH grant P05-MH090966 Keywords: Maternal Depression, neonatal, Amygdala, PFC, heart rate reactivity
242. Superficial White Matter Integrity in Autism Spectrum Disorders Marc-Antoine d'Albis1, Pamela Guevara2, Miguel Guevara2, Jean-François Mangin3, Cyril Poupon3, Duclap Delphine3, Laidi Charles4, Jennifer Boigontier5, Marion LEBOYER6, and Josselin Houenou7 APHP-France, 2Universidad de Conception, Chile, 3Neurospin, CEA, France, 4Inserm U955 eq15, Fondation FondaMental, GHU Mondor, Neurospin, CEA, France, 5Inserm U955 eq15, Fondation FondaMental, GHU Mondor, Neurospin, CEA,France, 6Inserm U955 eq15, Fondation FondaMental, GHU Mondor, France, 7Inserm U955 eq15, Fondation FondaMental, GHU Mondor, Neurospin, CEAFrance 1
Background: Autism spectrum disorders (ASD) are characterized by an atypical brain growth and abnormalities in the anatomical and functional connectivity. These abnormalities have been identified in the long-distance tracts (antero-posterior fasciculi, corpus callosum). Very few studies have explored shortdistance tracts (cortico-cortical U-shaped fibers), despite their importance in the local connectivity (between adjacent cortical gyri) and in the cognitive functions. Our work aims to study shortdistance anatomical connectivity in ASD subjects compared to controls. Methods: We included thirty ASD subjects and forty male controls without mental retardation. The subjects benefited from a 3T MRI (Neurospin), with anatomical and diffusion weighted sequences. We performed a whole brain tractography (Connectomist 2.0) and automatically segmented 63 short tracts. For each fasciculus, we extracted mean gFA (generalized Fractional Anisotropy), MD (Mean Diffusivity), AD (Axial Diffusivity) and RD (Radial Diffusivity). An ANCOVA was performed with gFA
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal
S99